Pathological angiogenesis, the growth of new blood vessels during a disease state, contributes to over 70 diseases, including cancer. The proposed studies are a Phase II SBIR grant application focused on the preclincal development of novel anti- angiogenic small molecules discovered using transgenic zebrafish. It is expected that these compounds may be useful in treating diseases associated with pathological angiogenesis. In the Phase I studies, a zebrafish assay for discovering new anti-angiogenic compounds was automated. A chemical compound library was screened using the zebrafish assay, and two known and one novel anti-angiogenic compounds were identified. In Phase II, these compounds will be tested in in vitro angiogenesis models and in in vivo cancer models to determine if the compounds inhibit the growth of human tumors. Zebrafish and mouse models of cancer wherein human tumor cells are implanted into the animal will be used. Additional chemical compound libraries will be screened to identify more novel anti-angiogenic compounds. Pathological angiogenesis, the growth of new blood vessels, contributes to over 70 diseases, including cancer, age-related macular degeneration, diabetic blindness, and rheumatoid arthritis. Novel anti-angiogenic compounds discovered in Phase I will be tested in relevant disease models to determine whether these compounds may be therapeutically useful. Moreover, chemical compound libraries will be screened using a transgenic zebrafish assay for angiogenesis to discover additional anti-angiogenic drugs. [unreadable] [unreadable] [unreadable]